This proposal requests support for a Keystone Symposia meeting entitled High-Throughput Structural Biology, organized by Ian A. Wilson, Aled M. Edwards, Tracy M. Handel and Andrej Sali, which will be held in Keystone, Colorado from January 22 - 27, 2012. Structural Biology continues to be one of the most prolific and informative ways to make biological and biomedical discoveries, and provides fundamental molecular insights into biological systems. The rapidly expanding numbers of sequenced genomes is providing structural biologists with a wealth of new opportunities and challenges to explore the enormous diversity of biological macromolecules and their relationships to function, evolution and disease. The meeting goal is to explore current advances and frontiers in structural biology and illustrate how high-throughput approaches in x-ray crystallography and NMR - in combination with hybrid methods using computational and other biophysical techniques (including CryoEM, Xray and Electron Tomography, SAXS, Mass Spectometry, Proteomics) - can be used to tackle topical and challenging problems in molecular, cellular and chemical biology. This symposium will focus on the variety of approaches and methodologies that are available to both structural biologists and biologists for investigation of biological systems and their component macromolecules and complexes. We will also address some topical issues of great relevance to the field through two open debates. The attendees will also have an opportunity to broaden their appreciation of the complex biological systems that can benefit from these current advances in structural biology via the sister meeting on Structure-Function- Biological Organization - which will share a keynote and two plenary sessions with this meeting. PUBLIC HEALTH RELEVANCE: The field of structural genomics encompasses cutting-edge experimental methods to determine the three- dimensional structure and function of proteins and other macromolecules. These technologies enable the scientific community to keep pace with the wealth of information derived from genome sequencing efforts. The Keystone Symposia meeting on High-Throughput Structural Biology will focus on how to address challenging proteins, biological systems and whole organisms, as well as how to fill the void in our knowledge of the protein universe that has become apparent from the vast numbers of genome sequences where the biological function is unknown.